Combination antiretroviral therapy for HIV-1 infection introduced in the last half-decade
has resulted in dramatic control of viremia in most patients and remarkable improvement
in morbidity and mortality. A sizable proportion of infected individuals, however,
fail to benefit from these agents or experience only temporary benefit because of
the emergence of resistant strains, unacceptable drug toxicity, or difficulties with
compliance. Although any step in the viral replication cycle is a potential target
for therapeutic intervention, currently available drugs target only two of these steps:
reverse transcriptase inhibitors block the stage early after viral entry when the
viral RNA genome is copied into DNA, and protease inhibitors block the protein processing
step carried out by the viral protease enzyme late in the replication cycle as virus
leave the host cell. New strategies that target other steps of infection are critically
needed. The last several years have yielded exciting advances in the understanding
of how HIV-1 enters its target cell, which have led to the development of promising
agents that block viral entry and are likely to be the next group of antiretroviral
drugs to become clinically available. This article addresses new insights into the
mechanism of HIV-1 entry, and focuses on prototype agents under study as representative
approaches that target specific steps of the entry process. More detailed information
of the structural biology and mechanisms of entry may be found in several excellent
recent reviews [
1
,
2
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3
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4
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Article info
Footnotes
☆This work was supported by grants AI 07632, AI 35502, and MH 61139 from the National Institutes of Health.
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© 2002 Elsevier Science (USA). Published by Elsevier Inc. All rights reserved.
